To avoid the high incidence of systemic allergic reactions observed with maximun tolerated doses of high potency and low potency extracts, a high potency extract was administered by an 8-dose weekly regimen to a fixed peak dose of 0.3 mg AgE (below the mean high potency peak dose of 4.3 mg AgE and the mean high potency systemic reaction dose of 0.9 mg AgE). This submaximal dose (approxi- mately 0.001 of concentrate) produced no severe systemic reactions, and the total symptom scores were significantly lower than those of an untreated control group but no IgG whole short ragweed antibody was detectable. A treated group receiving only 0.003 mg AgE (0.00001 of concentrate) had a total symptom score no different from the untreated controls. These data suggest that ragweed hayfever can be safely and effectively treated by submaximal doses of short ragweed in only eight injections and that comparative safety and efficacy of short wagweed extracts of differing potencies and compositions can be evaluated by administration of bioequivalent doses based on relative potency estimated by parallel-line bioassay.